A Phase I/II Study of Ultra-Hypofractionated Carbon-ion Radiation therapy for Low- and Intermediate-Risk Localized Prostate Cancer

Purpose: We report herein the 3-year results of a phase I/II prospective study of 4-fraction course of carbon-ion radiation therapy (CIRT) in patients with localized prostate cancer. Methods and Materials: The present was a single-institution, phase I/II prospective study including patients with low- or intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network criteria. Eligible patients were randomly assigned (1:1) to a 1- or 2-week schedule. Dose-limiting toxicities (DLTs) were defined as any genitourinary (GU) or gastrointestinal (GI) toxicity grade 3 or higher within 90 days of beginning CIRT. Ten patients were enrolled in each group, and the CIRT dose was increased in a stepwise manner if there were fewer than 4 cases of DLT. The initial CIRT dose was 36 Gy, followed by 40 Gy or 44 Gy. Low-risk patients did not receive androgen deprivation therapy (ADT), whereas intermediate-risk patients received 4 to 8 months of neoadjuvant ADT. Results: Between October 2018 and October 2020, 60 patients were enrolled in the present study and completed the treatment regimen. The median post-CIRT follow-up period was 42 months (range, 27-59 months). Of the 60 patients enrolled, 10 were in the low-risk group, and 50 were in the intermediate-risk group. Neither group experienced grade 3 or higher GI or GU adverse events; therefore, no dose-limiting toxicities were observed. The incidence of grade 2 GU toxicity within 90 days post CIRT was significantly higher in the 44 Gy group than in the 36 to 40 Gy group (P < .01, chi-square test with Yates correction). Biochemical failure was observed in 3 cases by 3 years post CIRT. No clinical recurrence or death because of prostate cancer occurred. Conclusions: Forty Gy in 4 fractions of CIRT may be appropriate for balancing the therapeutic effects and toxicity. Our findings support further investigations into the efficacy of this strategy. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY license.